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首页> 外文期刊>Pharmacogenomics >Role of the PACAP-PAC1-DISC1 and PACAP-PAC1-stathmin1 systems in schizophrenia and bipolar disorder: Novel treatment mechanisms?
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Role of the PACAP-PAC1-DISC1 and PACAP-PAC1-stathmin1 systems in schizophrenia and bipolar disorder: Novel treatment mechanisms?

机译：PACAP-PAC1-DISC1和PACAP-PAC1-stathmin1系统在精神分裂症和双相情感障碍中的作用：新的治疗机制？

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摘要

Two pituitary adenylate cyclase-activating polypeptide (PACAP)-signaling pathways linked to schizophrenia were reviewed. One pathway regulates the association between disrupted-in-schizophrenia 1 (DISC1) and DISC1-binding zinc-finger protein via PACAP, and the other inhibits stathmin1 expression via PACAP. PACAP reduces the association of the binding between DISC1 (a potential susceptibility gene for major psychiatric disease) and DISC1-binding zinc-finger protein (which binds to DISC1 near the translocation site) to induce neurite outgrowth. In addition, an association between SNPs of the PACAP or PAC1 genes and schizophrenia has been reported. On the other hand, expression of stathmin1, which induces abnormal axonal arborization, is upregulated in PACAP-knock out mice and the brains of patients with schizophrenia. Thus it is likely that, in the schizophrenic brain, the neural development depending on these two systems has been disturbed. The possibility that the regulation of these two systems could lead to new treatments for schizophrenia is also discussed.
机译：审查了两个与精神分裂症有关的垂体腺苷酸环化酶激活多肽（PACAP）信号通路。一种途径通过PACAP调节精神分裂症1（DISC1）和结合DISC1的锌指蛋白之间的关联，另一种途径通过PACAP抑制stathmin1表达。 PACAP降低了DISC1（一种主要的精神疾病的易感基因）与DISC1结合的锌指蛋白（与易位部位附近的DISC1结合）之间的结合关联，以诱导神经突生长。另外，已经报道了PACAP或PAC1基因的SNP与精神分裂症之间的关联。另一方面，在PACAP基因敲除小鼠和精神分裂症患者的大脑中，诱导异常轴突乔化的stathmin1的表达上调。因此，在精神分裂症的大脑中，依赖于这两个系统的神经发育很可能受到了干扰。还讨论了这两个系统的调节可能导致精神分裂症新疗法的可能性。

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